Cell surface glycoproteins and glycolipids are key recognition molecules involved in cell-cell interactions, differentiation and the cellular determination of tissue and species-specific phenotypic differences. Structural alterations in cell membrane glycoproteins and glycolipids are a direct consequence of the malignant transformations of a cell and are the likely cause of abnormal cell-cell, cell-substratum, or cell-ligand interactions characteristic of malignant cells which permit the establishment and metastatic spread of tumors. An understanding of the structures of normal membrane glycoproteins and glycolipids and of the comparable but structurally altered glycoproteins and glycolipids from chemically or virally transformed cells will identify the relevent biosynthetic lesions and guide investigations of the basic genetic alterations underlying the malignant process. Current research involves isolation of membrane glycoproteins from normal, preneoplastic, and neoplastic cell membranes by immunoprecipitation with monoclonal antibodies, characterization by computer facilitated analysis of two-dimensional IEF/SDS gel electrophoresis, and structural determination by high performance liquid chromatography (HPLC) and mass spectrometry. In the course of this work, monoclonal antibodies specific for human epithelial cells, for hamster fetal cells, and for chemically transformed hamster cell lines have been produced and a reproducible two-dimensional gel electrophoresis system for the analysis of glycoproteins has been developed. The anticarcinogenic lymphokine, lymphotoxin, has been shown to modulate glycoprotein biosynthesis in normal and transformed cells and to stimulate the synthesis in transformed cells of glycoproteins unique to normal cells. These studies have shown for the first time that transformed, tumorigenic cells synthesize normal and abnormal glycoproteins simultaneously. These results suggest that the transformation process has two different but significant effects on glycoprotein biosynthesis: one effect may cause molecular weight and negative charge, the other may cause control mechanisms to regulate inappropriate biosynthesis of structurally normal molecules.